Study of Efficacy and Safety of INC424 in Regularly Transfused Patients With Thalassemia.
Patients with severe thalassemia (thalassemia major) present with severe anemia that requires life-long transfusion therapy, spleen enlargement that may lead to increased transfusion requirement, and other serious complications as early death, growth retardation, bone deformations and iron overload due to blood transfusions. Splenectomy can significantly reduce transfusion requirement in thalassemia patients, but it is associated with an increased risk of serious complications such as sepsis and thrombosis. Preliminary preclinical and clinical data suggest that JAK2 inhibition, by reducing spleen size, may improve hemoglobin levels, thereby eliminating the need for splenectomy and reducing transfusion requirement and related iron overload.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Single Arm, Multicenter, Phase IIa Study to Explore the Efficacy and Safety of Ruxolitinib (INC424) in Regularly Transfused Patients With Thalassemia|
- Percent change of RBC (Red Blood Cell) transfusion requirement [ Time Frame: week 6 to week 30 ] [ Designated as safety issue: No ]Percent change in RBC transfusion requirement between week 6 and week 30 and the baseline period between week -24 and the day before first study drug administration.
- Change of spleen volume [ Time Frame: baseline, week 12, week 30 ] [ Designated as safety issue: No ]Change of spleen volume from baseline measured by MRI or CT at week 12 and week 30
- Change of pre-transfusion hemoglobin level [ Time Frame: baseline, week 1,2,3,4,6,12,18,24,30 ] [ Designated as safety issue: No ]Change of pre-transfusion hemoglobin level from baseline at each post-baseline visit
- Change of spleen length [ Time Frame: baseline, week 1,2,3,4,6,12,18,24,30 ] [ Designated as safety issue: No ]Change of spleen length from baseline over time measured by palpation
- Pharmacokinetics (PK) parameters of Cmin and C max [ Time Frame: baseline, week 2, 12 ] [ Designated as safety issue: No ]C min and C max (1h) of INC424 by actual dose administered
- Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: baseline, week 1,2,3,4,6,12,18,24,30 ] [ Designated as safety issue: Yes ]Adverse events (AEs), serious adverse events (SAEs), lab results, ECGs, vital signs
|Study Start Date:||February 2014|
|Estimated Study Completion Date:||February 2016|
|Estimated Primary Completion Date:||February 2016 (Final data collection date for primary outcome measure)|
Experimental: Study Treatment
Approximately thirty regularly transfused adult patients with thalassemia and spleen enlargement.
Drug: INC424 (ruxolitinib)
INC424 oral tablet (5 miligrams)
Please refer to this study by its ClinicalTrials.gov identifier: NCT02049450
|Contact: Novartis Pharmaceuticals||+41613241111|
|Contact: Novartis Pharmaceuticals|
|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|